Authored by Ann Liu, PhD
Medically Reviewed by Brian Koffman, MDCM (retired), MSEd
The Bottom Line:
The time-limited combination of duvelisib plus venetoclax was effective for treating relapsed / refractory CLL, but it also had significant side effects.
Who Performed the Research and Where Was it Presented:
Dr. Matthew Davids from Dana-Farber Cancer Institute and colleagues presented the results at the American Society for Hematology (ASH) Annual Meeting 2024.
Background:
Treatments that combine different targeted therapies are becoming more common as researchers look for new ways to treat relapsed / refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). Venetoclax plus rituximab is approved for use in relapsed / refractory CLL, but it is a two-year treatment regimen that includes six months of IV infusions. Researchers had seen promising results with the combination of PI3K inhibitor duvelisib and BCL2 inhibitor venetoclax in the laboratory, and they wanted to see if this all-oral combination could work for patients with relapsed / refractory CLL and Richter transformation with just one year on therapy.
Methods and Participants:
This was a phase 2 clinical trial of time-limited duvelisib plus venetoclax in patients with relapsed / refractory CLL or Richter transformation (syndrome). Patients who reached undetectable measurable residual disease (uMRD) after one year could discontinue treatment, and patients who still had detectable MRD could continue treatment with venetoclax.
Results:
- The study enrolled 29 patients with relapsed / refractory CLL and 9 patients with Richter transformation.
- This was a hard-to-treat group since 48% of patients had a TP53 mutation, and 45% of patients had already been treated with a BTK inhibitor.
- Common side effects included low neutrophil counts (86%), low platelet counts (58%), diarrhea (63%), nausea (55%), increased liver enzymes (45%), and hypertension (42%).
- 97% of patients with CLL responded to treatment, and 62% had a complete response.
- 41% of patients with CLL achieved uMRD in the bone marrow after one year.
- In patients with CLL, the three-year progression-free survival rate was 68%, and the overall survival rate was 89%.
- Three-year progression-free survival in TP53-aberrant (including those with del 17p) and post-BTKi patients was lower, at 47% and 46%, respectively.
- Three out of nine patients with Richter transformation experienced complete remission, and one patient proceeded to an allogeneic stem cell transplant.
Conclusions:
The combination of duvelisib plus venetoclax was effective for treating relapsed / refractory CLL, but it also had significant side effects. While it could be useful for some patients, the side effect profile of this combination is not for everyone. PI3K inhibitors such as duvelisib are not widely used for treating CLL, but they can still be useful for certain patients under the right circumstances and are FDA-approved. Other better-tolerated all oral combinations, such as acalabrutinib and venetoclax, should be approved soon, making this doublet even less relevant. Still, the more options, the better.
Links and Resources:
Watch the interview on the abstract here:
You can read the actual ASH abstract here: A Phase 2 Study of Duvelisib and Venetoclax in Patients with Relapsed or Refractory (R/R) Chronic Lymphocytic Leukemia (CLL) or Richter Syndrome (RS)
